EP4129313A2 - Pharmaceutical composition for the treatment of neurodermitis - Google Patents

Abstract

The invention relates to a pharmaceutical composition comprising passion flower herb in the form of a dry extract as an active ingredient and / or dried mussel foot concentrate as a further active ingredient for use in the treatment of neurodermatitis by oral or topical administration, with the proviso that passion flower herb in the form of a dry extract only together with dried mussel foot concentrate is applied topically. The effect is in some cases superior to that of conventional drugs known to date, since the side effects known from the prior art do not occur and the natural microflora of the skin and mucous membranes are not damaged but rather remain intact. In addition, the appearance of the skin is significantly improved.

Description

The invention relates to a pharmaceutical composition for treating neurodermatitis.

Background to the Invention

A large number of herbal medicines, so-called "phytopharmaceuticals", are already known, the effectiveness of which is usually based on several herbal ingredients. Herbal medicines are used on the basis of scientific knowledge to treat diseases (phytotherapy) and must meet the same requirements as classic chemical-synthetic medicines.

Naturopathic treatments have gained increasing importance alongside or in addition to traditional medicine. Medicinal herbs and medicinal plants, also known as medicinal plants, are used for medicinal purposes or to alleviate and treat numerous diseases for internal or external use. Herbal medicines can be used in a wide variety of forms, such as granules, tablets, capsules, dragees, lotions, tea preparations, bath additives, in cosmetics, dietary supplements, essential oils and much more. These basically have the same risks as all drugs, but are generally better tolerated than chemically synthesized active ingredients.

In contrast to chemical-synthetic active ingredients in classic medicines, where only one or a few active ingredients are present, herbal medicines usually contain a plant extract that is made up of many different individual substances that together determine the effect.

The active ingredients contained in the herbal medicinal product can also be the natural plant or parts thereof, which can be either unprocessed or processed in a suitable manner, for example comminuted. However, the herbal medicine is mostly based on the extract of the plant, is in particular an aqueous extract (macerate), aqueous-alcoholic extract or alcoholic extract of the whole plant or parts thereof. Fresh or dried plants or parts of plants can be used for this. The plant parts that are suitable for this depend on the selected medicinal plant and are, for example, flowers, bulbs, fruits, leaves, stems and/or roots of the plant. The active ingredients obtained represent the starting material for a herbal medicinal product and various dosage forms can be produced from them.

It is also known that medicinal plants can have a healing effect on completely different diseases and complaints due to their various ingredients. A few examples are given to explain:
Aloe vera is a recognized remedy for constipation, which can also be used externally as a gel or juice to heal wounds.

The roots of licorice are used as a remedy for stomach ulcers, respiratory infections and other ailments.

A well-known herbal medicine is St. John's wort. This is obtained from the dried shoot tips of St. John's wort (Hypericum perforatum) in the form of a total extract consisting of several active ingredients. It exhibits antibacterial and antiviral effects and has also become known for its antidepressant effects, which have been confirmed in clinical tests. However, the actual mechanism of action is still unclear.

There is a growing need for herbal medicines, so research in this area continues to be intense.

The passion flower is one of the classic medicinal plants. One of more than 500 species in the passionflower family, Passiflora incarnata L. is a perennial and climbing herb native to the United States, among other places. It is a well-known ornamental plant. Passion flower herb (Passiflorae herba) is already used as a herbal medicinal product. It consists of the dried, crushed or cut aerial parts of Passiflora incarnata L. Flowers and fruits may be present be. The herb of the passion flower therefore refers to all parts of the plant except the root.

The passion flower herb is also used as a dietary supplement.

Passionflower herb and preparations made from it have sedative, anxiolytic, and antispasmodic properties. The preparations of passion flower herb are used, among other things, as a sedative to calm down, to treat states of tension, inner restlessness, difficulty falling asleep, irritability and nervousness. A similar effect is attributed to the medicinal plants valerian, lemon balm, lavender and hops, which are also used in combination preparations with passion flower herb as a sedative.

In addition to an effect against restlessness, anxiety and sleep disorders, it is also said to be effective against liver problems. Application of the powder for local wound healing is also known.

Constituents of dried passionflower herb include flavonoids such as isovitexin, isoorientin, schaftoside, coumarins, glycosides, essential fatty acids, essential oil and carbohydrates.

Passion flower herb is commercially available in various mono preparations and is available, for example, in the form of coated tablets, extracts, drops, tea, powders or other forms of preparation. Well-known mono-preparations based on passion flower herb dry extract are, for example, "Valverde ^® Calming" and Sidroga ^® Calming Tea. Dried passionflower herb is also available in pharmacies and drugstores.

The preparations are usually taken two to four times a day. Possible undesirable effects include rare allergic reactions.

However, the use of passionflower herb in connection with the treatment of skin diseases by oral administration has not been reported so far.

Neurodermatitis, also known as atopic dermatitis or atopic eczema, is the most common chronic skin disease affecting people of all ages. It is a chronic inflammatory skin disease associated with itching. Itching (pruritus), a disturbed skin barrier, a predisposition to allergies and chronic inflammation of the skin and a disturbed skin flora (microbiome) are characteristic.

The disease often begins in infancy and childhood and typically progresses in phases, with phases with few or no symptoms alternating with phases of the disease. The disturbed skin barrier and reduced protective function of the skin cause a greatly increased sensitivity to irritation and non-specific stimuli, so that the skin is often dry, scaly and reddened, and the skin is also very itchy. Contact with germs or physical or chemical stimuli can easily lead to inflammation. Bacteria such as staphylococci, viruses such as herpes, or even fungi can intensify such infections.

It is therefore a chronic inflammatory but non-contagious skin disease for which there is often no cure, but many treatment options. The aim of the therapy is to make the symptoms disappear or at least to weaken and alleviate them and to prolong symptom-free phases.

The causes of neurodermatitis go back to various factors. Hereditary predisposition can play a role, since genes have been identified that have a supporting effect on the development of neurodermatitis, so that the skin cannot develop its barrier function properly. If unfavorable environmental influences are added, the disease can break out.

Typical symptoms of neurodermatitis are therefore generally dry skin with reddened, inflamed areas (eczema), which usually itch very badly; extensive Thickening and coarsening of the skin (lichenification) and nodules and pustules. The severe itching is very annoying and can lead to sleep disorders.

In addition to knowing and avoiding individual provocation factors, such as allergens, stress, rough clothing (e.g. wool), extensive or hot baths, intensive exposure to the sun, sweat, tobacco smoke, car exhaust fumes or the like, and particularly careful skin care, drug treatment is also common necessary. To date, only classic synthetic chemical drugs have been used for this purpose.

Antibiotics are not a suitable treatment. The drugs of choice are anti-inflammatory drugs, especially glucocorticosteroids ("cortisone preparations"). They are usually administered as creams, ointments or tablets, but usually only for a short time. The effect can only set in after a delay of several days. Long-term use of glucocorticosteroids causes the skin to become thinner or unwanted skin changes to result. These must therefore not be used regularly on a daily basis, and areas with thin skin should only be treated for a short time, if at all.

Another treatment option is calcineurin inhibitors. Even with constant use, these should not thin out the skin, but can lead to an increase in itching in the short term. The drug is not suitable for infants.

The treatment of moderate to severe cases of neurodermatitis with the IL-4 receptor blocker dupilumab, which is injected every two weeks, has also become known. However, eye problems ranging from mild irritation to more severe inflammation can occur as side effects.

Another treatment option is the administration of ciclosporin A, which can show a rapid onset of action, but regularly leads to a rebound effect after stopping, ie an increased recurrence of the symptoms of the drug-treated disease after stopping the drug drug. Side effects are increased blood pressure, nephrotoxicity and a greatly increased risk of white skin cancer.

Furthermore, the following suggestions for the treatment of skin diseases have become known from the prior art:
The US 2016/0 074 312 A1 relates to a composition containing as active ingredient a peptide and a sugar extract of passion flower seeds and optionally a suitable excipient, the peptide and sugar extract being obtained by enzymatic hydrolysis in the presence of at least one protease and at least one carbohydrase. The composition is used cosmetically, pharmaceutically, dermatologically or as a dietary supplement. The treatment of atopic dermatitis is also mentioned among a large number of possible uses. The ingredients of the passion flower seeds are changed chemically, biochemically or biotechnologically: In example 1 of the US 2016/0 074 312 A1 enzymatic hydrolysis is carried out, then hydrolysis with an acid protease, followed by heat treatment in which the enzymes are denatured. These processes mean significant changes, chemical transformations and sometimes even the destruction of the natural ingredients. This is in contrast to the present invention, according to which the natural ingredients should be preserved, no chemical, biochemical or biotechnological treatments of the plant parts are carried out and the passion flower extract is obtained in the most gentle way possible so as not to change the ingredients. Added proteases and carbohydrases should also not be present in the passion flower dry extract of the present invention.

The US 2019/0 209 631 A1 describes a lipid extract of Passiflora seeds, Passiflora incarnata, Passiflora edulis or mixtures thereof. It is a concentrated oil, among a multitude of possible uses, mentioning atopic dermatitis. The lipid extract is obtained by molecular distillation of crude or refined Passiflora oil. A lipid extract has only non-polar, oil-soluble ingredients and therefore has a completely different composition of ingredients than an aqueous/alcohol-containing extract, which only has polar and water/alcohol-soluble ingredients; there is therefore generally a completely different spectrum of action. A dry extract of passion flower herb, which is obtainable from a lipid extract is not used in the present invention.

Further describes Manez, S. et al., Selected Extracts from Medicinal Plants as Anti-Inflammatory Agents, in: Planta Med., 1990, Vol. 56, p. 656 , an aqueous extract of Perna canaliculus (green-lipped mussel, green-lipped mussel or New Zealand mussel), where an aqueous extract is obtained from the whole mussel. Edema is induced in paws of Swiss albino mice by subcutaneous injection of carrageenan solution. In order to prevent the edema, the mice were injected with the extract intraperitoneally 1 hour before the artificial edema production. Oral or topical administration is not described. An aqueous extract of New Zealand mussels is used and not a concentrate. Only water-soluble ingredients are contained in the aqueous extract used. The treatment of edema that occurs, ie accumulations of fluid in the tissue, is not related to neurodermatitis treatment of the skin. In addition, New Zealand mussels are preferably not used according to the invention.

Furthermore, the US 2020/0 353 024 A1 a Candida albicans anti-inflammatory composition that features heat-killed Candida albicans combined with a neuroprotective supplement. The neuroprotective supplement is, for example, a positive allosteric modulator of the GABA A receptor, such as a herbal drug, among a variety of possible plants including passionflower whole or plant extract. The composition is also administered, inter alia, in the case of atopic dermatitis. Candida albicans, particularly heat-killed Candida albicans, is not included in the pharmaceutical composition of the present invention.

Also describes the WO 00/53198 A1 the use of a lipid extract of Perna canaliculus or Mytulis edulis administered orally or topically in a wide range of diseases and disorders such as dermatitis or atopic eczema. The lipid extract is obtained by supercritical fluid extraction of freeze-dried mussel powder with CO ₂ . It is only about the oil-soluble ingredients, although it is questionable whether these ingredients survive the freeze-drying procedure unscathed. In the examples, only the Efficacy demonstrated in bronchial asthma. A lipid extract of mussel or mussel foot is not used in the present invention.

The WO 00/71140 A2 refers to a composition containing N,N-dimethylglycine and Perna canaliculus, for example, as freeze-dried minced whole mussel. The composition is also administered orally, among other things, against dermatitis. Neither the mussel foot for preparing the concentrate nor the mussel foot concentrate in the pharmaceutical composition of the present invention shall be freeze-dried. Furthermore, N,N-dimethylglycine is not used in the pharmaceutical composition of the present invention.

Finally revealed the CN 104 336 727 A a type of milk-flavored drink made e.g. B. is used to improve eyesight and comes from traditional Chinese medicine. In addition to passion flower juice, dried mussels and sometimes a number of very exotic ingredients such as Dendrobium candidum (a type of orchid), tangerine peel juice, pork liver, pomegranate leaf, lotus, peanut rice, lily and the like are also used. In the present invention, the only active substances are passion flower dry extract and/or mussel foot concentrate, other active substances are not contained in the pharmaceutical composition, but only optionally one or more excipients.

Many people suffering from neurodermatitis, especially children, find it tedious, time-consuming and also unpleasant to have to repeatedly apply active ingredient ointments and creams to the skin, sometimes over many years. Therefore, there is a great interest and a great need for treating neurodermatitis in a systemic manner, in particular by oral administration of a drug. Furthermore, none of the side effects known from the prior art should occur, even with long-term use of the drug. In particular, the drug should be as well tolerated as possible and show only very few side effects.

Detailed description of the invention

• wobei das Passionsblumenkraut in Form eines Trockenextrakts erhältlich ist durch
  • Ernten, Zerkleinern und Trocknen des Passionsblumenkrauts in Form der Pflanzenteile der Passionsblume, ohne Wurzel;
  • Durchführen einer Fest-Flüssig-Extraktion der getrockneten Pflanzenteile unter Verwendung von einem Extraktionsmittel, ausgewählt aus Wasser, Alkohol oder Alkohol-Wasser-Gemischen bei Raumtemperatur (25°C) oder einer Temperatur im Bereich zwischen Raumtemperatur (25°C) und 78°C, mit oder ohne Rühren und/oder Schütteln;
  • Abtrennen der Pflanzenteile vom Extraktionsmittel durch Dekantieren oder Filtrieren, und
  • Abdampfen des Extraktionsmittels unter Erhalt eines Trockenextrakts des Passionsblumenkrauts; und
• wobei das getrocknete Miesmuschelfuß-Konzentrat zerkleinerten und getrockneten Miesmuschelfuß von Miesmuscheln darstellt, mit der Maßgabe, dass Passionsblumenkraut in Form eines Trockenextrakts nur zusammen mit getrocknetem Miesmuschelfuß-Konzentrat topisch verabreicht wird und dass Candida albicans und N,N-Dimethylglycin in der pharmazeutischen Zusammensetzung nicht enthalten sind.

The problem described is solved by a pharmaceutical composition comprising
Passionflower herb in the form of a dry extract as an active ingredient and/or dried mussel foot concentrate as another active ingredient, for use in the treatment of neurodermatitis by oral or topical administration,

• wherein the passion flower herb is available in the form of a dry extract from
  • Harvesting, crushing and drying the passion flower herb in the form of the plant parts of the passion flower, without the root;
  • Carrying out a solid-liquid extraction of the dried plant parts using an extractant selected from water, alcohol or alcohol-water mixtures at room temperature (25°C) or a temperature ranging between room temperature (25°C) and 78°C , with or without stirring and/or shaking;
  • separating the plant parts from the extractant by decantation or filtration, and
  • evaporating the extraction agent to obtain a dry extract of the passion flower herb; and
• wherein the dried mussel foot concentrate is crushed and dried mussel foot of mussels, provided that passionflower herb is topically administered in the form of a dry extract only together with dried mussel foot concentrate and Candida albicans and N,N-dimethylglycine are not included in the pharmaceutical composition are.

• Passionsblumenkraut in Form eines Trockenextrakts;
• Passionsblumenkraut in Form eines Trockenextrakts und getrocknetes Miesmuschelfuß-Konzentrat; oder
• getrocknetes Miesmuschelfuß-Konzentrat.

According to the present invention, a pharmaceutical composition is therefore provided which is based on naturally occurring substances, in particular can be produced on the basis of a medicinal plant and/or animal proteins. The pharmaceutical composition can have the following active ingredients:

• passion flower herb in the form of a dry extract;
• passion flower herb in the form of a dry extract and dried mussel foot concentrate; or
• dried mussel foot concentrate.

The pharmaceutical composition is administered either orally or topically (by applying to the skin), however, passionflower herb in the form of a dry extract is not topically administered as the sole active ingredient in the pharmaceutical composition; when administered topically, the passion flower herb in the form of a dry extract is always administered together with dried mussel foot concentrate. However, dried mussel foot concentrate can also be administered topically as the sole active ingredient in the pharmaceutical composition. For oral administration, both passion flower herb comes in the form of a dry extract; a combination of passion flower herb in the form of a dry extract and dried mussel foot concentrate; as well as dried mussel foot concentrate.

An active ingredient of the pharmaceutical composition according to the invention is therefore a dry extract of the passion flower herb. Passion flower herb dry extract is referred to herein as "one active ingredient" although it contains a variety of different substances. Since all of the extracted herbal ingredients provide the effect according to the invention, this is simply described as "one active ingredient".

The passion flower herb represents the plant parts of the passion flower (Passiflora incarnata L.), apart from the root. It is therefore possible to harvest all plant parts from the plant itself - apart from the root - to crush them, for example to cut them into small pieces, and to dry. Preference is given to passion flowers from controlled organic cultivation. Alternatively, dried passion flower herb is also commercially available and can be purchased, for example, in a pharmacy or drugstore.

An extract is made from the dried passion flower herb using an extraction agent. The extraction agent can be selected from water, alcohol-water mixtures or alcohol. Alcohol-water mixtures, in particular ethanol-water mixtures containing 50% ethanol (v/v), are particularly preferred. It can be extracted at room temperature (25°C) or elevated temperature up to a maximum of 78°C (boiling point of ethanol). To lower the temperature and gentle extraction, it is also possible to do this in a vacuum to be worked. Therefore, a solid-liquid extraction is carried out with the solid parts of the plant and the liquid extractant. The plant parts - fresh or in dried form - can also simply be left in the extractant for a longer period of time with or without stirring and/or shaking. Depending on the amounts and type of dried passionflower herb used, the extraction agent selected and the extraction conditions, the extraction can take several hours, days or even several weeks.

The liquid extract obtained is separated from the extracted passion flower herb, e.g. by decantation or filtration, and the solvent contained is removed by evaporation or evaporation, e.g. in vacuo. Hereby the dry extract of the passion flower herb is obtained, which serves as a basis for the pharmaceutical composition.

The dry extract of the passion flower herb is a concentrate of the plant components in a solid form, which is hygroscopic and can be sensitive to light in solution. As a rule, extracts of 5:1 to 7:1 or even up to 10:1 are provided. This means that with a 5:1 extract: 5 parts of the plant are obtained as 1 part of the dry extract from the extraction and drying. For example, a 5:1 extract: from 5500 mg of passion flower herb will yield 1100 mg of extract.

In addition to being produced from the fresh plant, a corresponding dry extract can also be purchased directly from retailers, for example from pharmacies or drugstores. It has been found that the quality of the commercially available dry extracts is well suited for the production of a pharmaceutical composition for the treatment of neurodermatitis.

It is important for the present invention that the solid plant parts of the passion flower herb are not subjected to any treatment that alters the ingredients, in particular no chemical, biochemical or biotechnological treatment, such as an enzymatic hydrolysis, ie are used untreated. The plant parts from nature are called such used. Of course you can wash the parts of the plant briefly (a few minutes) with water to remove dirt; however, this does not represent a treatment within the meaning of the present invention, since the plant constituents are not changed as a result. According to the invention, the natural ingredients in the dry extract should therefore not be altered by chemical or biological additives and should remain intact. The liquid extract and its dry extract are then obtained from the untreated parts of the plant, whereby the passion flower extract is obtained as gently as possible so as not to change the ingredients. A chemical, biochemical or biotechnological treatment during the production of the dry extract is therefore completely undesirable and does not take place. This would change the ingredients of the plant parts and thus significantly reduce or even destroy their effectiveness. An additional heat or cold treatment during the preparation of the dry extract other than the solid-liquid extraction of the passion flower herb, such as additional heating or freeze-drying, should also not be carried out in order not to damage the ingredients. Any treatment that affects the ingredients should therefore be avoided.

After several years of tests, it was found that the dry extract of the passion flower herb can be used successfully as the sole active ingredient in a pharmaceutical composition for the treatment of neurodermatitis. It can be administered orally; topical administration as the sole active substance is ruled out according to the invention.

In tests with a pharmaceutical composition comprising the dry extract of the passion flower herb as the sole active ingredient for oral administration, reduced redness and significantly reduced itching were found in the treatment of neurodermatitis. In general, a clear calming of the inflamed skin areas was observed. Overall, the dry extract of the passion flower herb resulted in a significant improvement in the complexion of the skin in neurodermatitis. The dry extract of the passion flower herb has a particularly positive effect on the skin in general and in particular on skin affected by neurodermatitis - which is completely in contrast to the anti-inflammatory drugs otherwise administered, such as glucocorticoids, which can damage the skin, especially with prolonged use.

Undesirable side effects were not found in the multi-year trials.

Another active ingredient of the pharmaceutical composition of the present invention, which can be used alone or together with the dry extract of passionflower herb, is a dried mussel foot concentrate. As with passionflower herb dry extract, dried mussel foot concentrate is referred to herein simply as "an active ingredient", although several different substances, particularly proteins, are present, but together they provide the effect, i.e. act as one active ingredient.

The dried mussel foot concentrate is obtained from mussels. Mussels, also known as scallops or blue mussels, are edible mussels (Mytilidae) that are considered a delicacy in many countries. They have become known for their blue and black skin and firm flesh. The name of this mussel comes from the old German word for moss, since the mussels form large carpets in their habitat on the sea floor, which are visually reminiscent of moss.

The habitat of the mussel is, among other things, in the North Sea off Denmark, Belgium, the Netherlands and the Atlantic coasts off France, Spain and Portugal. You can also find them off German coasts; in the Wadden Sea of the North Sea coast it forms large natural banks. 95 percent of world mussel production comes from aquaculture, with the largest producers being China and the EU. Mussels from New Zealand, in particular green-lipped mussels, are preferably not used according to the invention.

The mussel is mainly found in the tidal and shelf areas of the sea. The mussels have a shell made up of two calcareous valves held together. Inside the shell is the body of the mollusk. Mussels have gills and can therefore be permanent live under water. This is how they get the oxygen and nutrients from the water.

There is usually a strong current in the living area of the mussels. In order to be able to survive in these regions and not be washed out to sea, the mussel excretes threads with which it holds on. Between the mussel's gills is a muscular foot with the byssus gland. This gland produces the so-called byssus threads with the help of the protein contained in the mussel; these are threads or filaments that allow the mussel to hold on. The mussels use these threads or filaments to attach to rocks; to adhere to boats or other surfaces in the intertidal zones even in strong ocean currents.

The mussel foot is therefore a special organ with which the mussels can hold on and also move.

In the present invention, a dried mussel foot concentrate is used as an active ingredient. In particular, mussels of the genus Mytilus edulis are used. The mussel foot concentrate is obtained directly from mussels that are as fresh as possible by removing the foot, crushing and drying the material obtained.

The mussels from which the foot is removed preferably come from a nature reserve, such as the Wadden Sea nature reserve off Sylt, since the environmental conditions there are particularly good. The resulting dried mussel foot concentrate consists mainly of proteins, which are characterized by special properties that come into play in the treatment of neurodermatitis.

It is important for the present invention that the mussel foot is not subjected to any treatment that changes the ingredients, in particular no chemical, biochemical or biotechnological treatment, such as an enzymatic hydrolysis, ie is used untreated. The mussel foot from nature is used as such in an untreated form. Of course you can wash the shell with water to remove dirt removed; however, this does not represent an undesirable treatment within the meaning of the present invention, since the ingredients are not changed as a result. According to the invention, the natural ingredients in the mussel foot concentrate should therefore not be altered by chemical or biological additives and should remain intact. The concentrate is not an extract, but contains all the ingredients of the mussel foot in an untreated form. A chemical, biochemical or biotechnological treatment before or during the production of the concentrate is therefore completely undesirable and does not take place. This would change the ingredients and thus significantly reduce or even destroy their effectiveness. An additional heat or cold treatment before or during the preparation of the concentrate, such as heating or freeze-drying, should also not be carried out in order not to adversely affect the ingredients. Any treatment that affects the ingredients should therefore be avoided.

After several years of trials, it was found that mussel foot concentrate can be used successfully as the sole active ingredient in a pharmaceutical composition for the treatment of neurodermatitis. It can be administered orally or topically. The tests confirm that a patient suffering from neurodermatitis, who is treated with a pharmaceutical composition comprising mussel foot concentrate, experiences a significant calming of the inflamed skin, and that the firmness, reduction of flaking and smoothing of the skin are observed. Overall, a significant improvement in the appearance of the skin in neurodermatitis is obtained by a pharmaceutical composition comprising the mussel foot concentrate. A pharmaceutical composition comprising the mussel foot concentrate as the only active ingredient has a particularly positive effect on the skin in general and in particular on the skin areas affected by neurodermatitis - which is in complete contrast to the usual anti-inflammatory drugs such as glucocorticoids, which the skin, especially in prolonged use, can cause damage.

Undesirable side effects were not found in the multi-year trials.

In the present invention, a combination preparation of dry extract of passionflower herb and dried mussel foot concentrate, orally or topically, together in one dosage form (so-called fixed-dose combination, wherein the two active ingredients to be combined are present simultaneously in the same pharmaceutical formulation) or in two same or different dosage forms (free dose combinations, where the two active ingredients to be combined are in separate pharmaceutical formulations).

For example, for oral administration, both active ingredients can be present simultaneously in a capsule or tablet, or one active ingredient is in a capsule and the other active ingredient is in a capsule or tablet.

For example, for topical administration, both active ingredients can be present simultaneously in a tincture or cream, or one active ingredient is in a tincture and the other active ingredient is also in a tincture or cream.

The combination of dry extract of the passion flower herb and dried mussel foot concentrate, either in the form of a fixed dose combination or free dose combination, both for oral and topical administration, shows a clear calming of the inflamed skin in the clinical picture of neurodermatitis, a strengthening of the skin and reduced scaling of the skin as well as a smoothing of the skin, whereby an existing redness decreases and the itching is significantly reduced. In addition, a particularly positive influence on skin elasticity, skin firmness, the skin's water balance and cell differentiation and proliferation is observed. A significantly improved elasticity and a significantly improved firmness of the skin can be achieved, while at the same time the water loss of the subcutaneous skin tissue is greatly reduced. Overall, a significantly improved complexion is observed. It seems that the interaction of the two active ingredients, ie the dry extract of the passion flower herb and the dried mussel foot concentrate, leads to an even better treatment success for neurodermatitis than both active ingredients alone, ie a synergistic effect is assumed.

The pharmaceutical composition may be administered orally or topically, with the limitation described that the dry extract of passionflower is not topically administered as the sole active ingredient.

In contrast to the so-called systemic administration of a drug, "topical" administration is understood here to mean local therapy in which the active ingredient or active ingredients are applied where they are intended to have a therapeutic effect. In the present case, topical administration is topical and external application to the skin. This can be done with any dosage form known to those skilled in the art for this purpose. Such formulations are provided in a liquid, semi-solid or solid dosage form and may, for example, be in the form of a solution, especially a tincture, drops, oil, suspension, especially a shake, emulsion, lotion or milk, cream or paste or the like. Preferred topical administration forms are tinctures, especially in the form of drops, or a cream.

The pharmaceutical composition comprising the dry extract of the passion flower herb and the dried mussel foot concentrate or only the dried mussel foot concentrate can therefore be applied locally (topically) to the skin in the selected administration form or formulation.

Tincture for topical administration is understood here to mean an aqueous or hydroalcoholic mixture with the dried mussel foot concentrate and optionally the dry extract of the passion flower herb. Solvents are water and water/alcohol mixtures. A solution is usually formed, in which case - prior to administration - undissolved components can be removed by filtration. "Solution" is not understood here to mean a homogeneous, clear liquid, but any form of mainly liquid mixture; this also includes a dispersion or suspension.

Ready-made tinctures are also available for purchase and come in a variety of strengths. For example, the tincture Ceres Passiflora Incarnata mother tincture from the company CERES Heilmittel is suitable for topical administration GmbH or the tincture Naturalma passion flower (Passiflora incarnata), herb with flowers, alcohol-free mother tincture, from Naturalma srl, Bologna.

Another route of administration is oral administration. This represents a systemic administration since the entire body is subjected to the therapy. Suitable preparations for oral administration of the active substance(s) according to the present invention include, for example, tablets, in particular film-coated tablets, pills, coated tablets, lozenges, pellets, capsules, in particular hard or soft capsules, powders, granules, solutions, in particular tinctures in the form of drops, Suspensions, dispersions or emulsions. Film-coated tablets, capsules, tinctures, in particular drops, are preferred. The pharmaceutical composition comprising the dry extract of the passion flower herb and the dried mussel foot concentrate or only the dried mussel foot concentrate or only the dry extract of the passion flower herb can therefore be administered orally in the selected dosage form or formulation.

Tincture for oral administration is understood here to mean an aqueous or hydroalcoholic mixture with the dry extract of the passion flower herb and/or dried mussel foot concentrate. The above comments on topical tincture apply accordingly.

It may also be advantageous when two different oral dosage forms are combined. For example, in addition to a capsule or tablet administered, e.g., 1 to 3 times daily, a tincture may be administered, e.g., 1 to 3 times daily. In this way, the dosage amount can also be easily varied for a specific patient.

For therapeutic use of the pharmaceutical composition, any conventional dosage form suitable for oral or topical administration can be employed. The preferred route of administration depends, inter alia, on the severity of the neurodermatitis and the condition of the patient.

The administration of the active ingredient(s) of the invention is effected in a suitable pharmaceutical composition in which the active ingredient(s) alone are present or in which the active ingredient(s) are present together with conventional pharmaceutical acceptable excipients are present. In the pharmaceutical composition of the present invention, the only active ingredients are passion flower dry extract and/or mussel foot concentrate, other active ingredients are not included in the pharmaceutical composition. In addition to the active ingredients in the form of passion flower dry extract and/or mussel foot concentrate, one or more excipients can optionally be present in the pharmaceutical composition.

Examples of pharmaceutically acceptable excipients include carriers, customary additives, diluents, binders, disintegrants and the like, and combinations thereof. In the context of the present invention, the term "pharmaceutically acceptable" means excipients that can be used for the treatment described and are not undesirable from a medical point of view, do not show any disadvantageous and/or harmful influence in the context of medical administration to a user, for example no irritation , allergies or other problems in the user considering the severity of the impairment or illness and the need for treatment.

Such pharmaceutically acceptable excipients as well as methods for preparing pharmaceutical compositions for the various routes of administration are well known to those skilled in the art.

Suitable tablets can be prepared, for example, by mixing the active ingredient(s) with known excipients, for example one or more diluents, one or more binders, one or more glidants or lubricants, optionally one or more disintegrants or disintegrants and optionally other additives. Some of the excipients may have two or more functions at the same time, e.g., acting as a binder, diluent and filler.

Any diluent conventionally employed in tablets may be used. Suitable diluents are, for example, lactose, in particular lacose monohydrate, cellulose and derivatives such as cellulose powder, starches and derivatives thereof, glucose, oligosaccharides such as sucrose, or maltodextrin calcium carbonate. Preferred diluents are lactose monohydrate and cellulose powder.

Any glidant or lubricant commonly employed in tablets can be used. Examples of suitable lubricants are silicon dioxide, in particular highly disperse silicon dioxide, talc, sodium dodecyl sulfate, stearic acid and salts thereof, such as magnesium stearate. Preferably the magnesium stearate is a vegetable product such as a magnesium salt of fatty acids derived from sunflower oil.

Any disintegrant commonly used in tablets can be used as the disintegrant. A suitable disintegrant is, for example, croscarmellose sodium or corn starch.

Any known binder commonly used in tablets can be used. Binders are, for example, naturally occurring or partially or fully synthetic polymers selected from cellulose and derivatives thereof, e.g., hypromellose (cellulose hydroxypropylmethyl ether), starch and derivatives thereof, tragacanth and gelatin. The gelatin is preferably not an animal product and is derived from plant sources, for example red algae. Vegan gelatine is therefore preferred.

Optionally, coloring additives such as titanium dioxide (food additive E 171), copper-containing complexes of chlorophylls and chlorophyllins (food coloring E 141), preferably of vegetable origin, or iron oxide pigments can also be used in the tablets.

The tablets may be coated, having one layer, such as in a film-coated tablet, or multiple layers. Coatings are selected, for example, from Kollidon, shellac, waxes such as carnauba wax, gum arabic, talc, titanium dioxide, sugar, hydroxypropylmethylcellulose and mixtures of these and can also contain additional auxiliaries. A film coating comprises, for example, a film-forming agent, a plasticizer, a lubricant, and optionally one or more pigments. An exemplary film coating composition may include: Hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG), talc, titanium dioxide and optionally iron oxide, including red and/or yellow iron oxide.

Capsules containing the active substance or substances can be produced, for example, by mixing the active substance or substances with suitable pharmaceutically acceptable excipients and packaging them in hard or soft capsules. The suitable pharmaceutically acceptable excipients are known to the person skilled in the art and essentially correspond to the pharmaceutically acceptable excipients which have been described in detail in connection with tablets.

Other pharmaceutically acceptable excipients that are used in particular for liquid preparations are, for example, vegetable oils and waxes such as jojobal oil, olive oil, almond oil, shea butter; essential oils; emulsifiers, in particular emulsifiers of vegetable origin, such as temulsifier (a vegetable emulsifier from palm oil); vitamins such as D-alpha-tocopheryl succinate (vitamin E); Solvents such as distilled water, alcohol such as ethanol, glycerin, phenethyl alcohol and the like. Other pharmaceutically acceptable excipients not explicitly mentioned here but known to those skilled in the art may also be used.

Liquid preparations, such as solutions, in particular tinctures, or the like are produced in the usual way, e.g. with the addition of solvents, in particular water for pharmaceutical purposes, i.e. distilled water, or water/alcohol mixtures to the active substance or substances, in particular the Dry extract of passion flower herb and/or dried mussel foot concentrate and optional subsequent filtration of the solution. Alcohols used are, for example, ethanol or glycerol.

According to another embodiment, a commercially available tincture can be used as the pharmaceutical composition, optionally diluted with distilled water. Also, since a tincture is commercially available only for the passion flower herb, the dried mussel foot concentrate can also be optionally added to the commercially available tincture in an appropriate amount when preparing a combination preparation for oral administration or topical administration should. The tincture with the active ingredient(s) and the solvent can be used directly as a pharmaceutical composition.

In individual cases it can be advantageous if the pharmaceutical composition is free from aromas, colorings and stabilizers, lactose-free, gluten-free and/or free from preservatives.

When excipients are of vegetable and non-vegetable origin, it can be advantageous if excipients are selected such that they are of vegetable origin. According to one embodiment, it can be preferred if only herbal excipients are used in the pharmaceutical composition.

In particular, it can be preferred if only vegan excipients are used, i.e. excipients originating from animals or excipients originating or derived from animal products are then not included. This can be an advantage with regard to possible allergies.

The dosage of the active ingredient(s) according to the invention is of course highly dependent on the selected route of administration and the clinical picture of the neurodermatitis to be treated.

For oral administration, the preferred (dosage) amount of passionflower herb dry extract present in the pharmaceutical composition per solid oral dosage form (eg contained in a tablet or a capsule) is in the range 45 to 500 mg or 90 to 100 mg 450 mg or 100 to 450 mg or 150 to 450 mg or 200 to 450 mg or 250 to 450 mg. Preferred (dosage) amounts in the pharmaceutical composition (e.g. per tablet or capsule) are therefore for example 45 mg, 50 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg or 500 mg, in particular 350 or 400 mg, of the dry extract of the passionflower herb. Oral administration of the pharmaceutical composition can be, for example, up to five times a day, ie, one to five times a day, or one to four times a day, or one to three times a day, or one to two times a day, or once a day. The total dose is then about 45 to 2500 mg or 90 to 2250 mg or 100 to 2000 mg or 225 to 1800 mg or 400 to 1500 mg for one patient per day. The dosage is selected depending on the patient's body weight and the severity of the neurodermatitis. This depends on each individual case.

For oral administration, the preferred (dosage) amount of the dried mussel foot concentrate present in the pharmaceutical composition per solid oral dosage form (e.g. contained in a tablet or a capsule) is in the range of 1 mg to 50 mg, 1 to 45 mg, 1 to 40 mg, 1 to 35 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg or 2 to 12 mg or 3 to 10 mg. Preferred (dosage) amounts in the pharmaceutical composition (e.g. per tablet or capsule) are therefore for example 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg or 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27mg, 28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg, 39mg, 40mg, 41mg, 42mg, 43mg , 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg or 50 mg dried mussel foot concentrate. The total dose is then, for example, about 5 to 250 mg or 10 to 200 mg or 15 to 150 mg or 15 to 100 mg for one patient per day.

The active ingredient(s) in the pharmaceutical composition for oral administration may be the dry extract of passion flower herb and/or the dried mussel foot concentrate. Preferably, the active ingredients in the pharmaceutical composition for oral administration are the dry extract of the passion flower herb and the dried mussel foot concentrate.

• Passionsblumenkraut in Form eines Trockenextrakts und optional Hilfsstoffe; oder
• Passionsblumenkraut in Form eines Trockenextrakts und getrocknetes Miesmuschelfuß-Konzentrat und optional Hilfsstoffe; oder
• getrocknetes Miesmuschelfuß-Konzentrat und optional Hilfsstoffe.

According to one embodiment, a capsule is selected as the dosage form for the pharmaceutical composition for oral administration. The capsule has the following active ingredients as a pharmaceutical composition:

• Passion flower herb in the form of a dry extract and optional excipients; or
• passion flower herb in the form of a dry extract and dried mussel foot concentrate and optional excipients; or
• dried mussel foot concentrate and optional excipients.

The active ingredient(s) can be present in the capsule itself, i.e. contained without auxiliary substances.

The capsule preferably comprises the following components: - Passion flower herb dry extract: (for example a 5:1 extract) 5.0 - 99.9% by weight and - dried mussel foot concentrate: 0.1 - 10.0% by weight, or - Dry extract of passion flower herb: 5.0 - 100% by weight or - dried mussel foot concentrate: 0.1 - 100% by weight (for the dried mussel foot concentrate preferably based on mussels from the nature reserve Wadden Sea off Sylt)
and optionally the following excipients: - Lactose monohydrate 0 - 45% by weight - cellulose powder 0 - 45% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight the amounts of the respective components being chosen such that the total weight of the components does not exceed 100% by weight.

• Passionsblumenkraut in Form eines Trockenextrakts und Hilfsstoffe; oder
• Passionsblumenkraut in Form eines Trockenextrakts und getrocknetes Miesmuschelfuß-Konzentrat sowie Hilfsstoffe; oder
• getrocknetes Miesmuschelfuß-Konzentrat und Hilfsstoffe.

Another preferred dosage form for the pharmaceutical composition for oral administration is a tablet, especially a film-coated tablet. The tablet has the following active ingredients as a pharmaceutical composition:

• Passion flower herb in the form of a dry extract and excipients; or
• Passion flower herb in the form of a dry extract and dried mussel foot concentrate and excipients; or
• dried mussel foot concentrate and excipients.

According to one embodiment, a tablet has the following components: - Passion flower herb dry extract: preferably 9.0 - 93.4% by weight, (e.g. a 5:1 extract) 5.0 - 93.4% by weight, and - dried mussel foot concentrate: 0.1 - 10% by weight, or - Dry extract of passion flower herb: 5.0 - 93.5% by weight or - dried mussel foot concentrate: 0.1 - 93.5% by weight (for the dried mussel foot concentrate preferably based on mussels from the nature reserve Wadden Sea off Sylt)
and the following excipients: - Lactose monohydrate 2.5 - 45.0% by weight - cellulose powder 3.5 - 45.0% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0.5 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight, the amounts of the respective components being chosen such that the total weight of the components does not exceed 100% by weight.

The tablet can be provided with an additional layer composed, for example, of Kollidon, shellac, gum arabic, talc, titanium dioxide, sugar and hydroxypropylmethylcellulose or mixtures of these.

When a liquid dosage form is used for oral administration, such as a tincture, e.g. in the form of drops, an appropriate amount of passionflower herb dry extract and/or mussel foot concentrate may be employed in the pharmaceutical composition, depending on the passionflower herb dry extract used can be very different:
For an oral liquid dosage form, such as a tincture, the dosage level is within the range given above. Therefore, to prepare a liquid dosage form, about 10 to 100 g of the dry extract of the passionflower herb is used. Preferred amounts are, for example, 10 g, 15 g, 20 g, 25 g, 30 g, 35 g, 40 g, 45 g, 50 g, 55 g, 60 g, 65 g, 70 g, 75 g, 80 g, 85 g g, 90 g, 95 g or 100 g of the dry extract of the passionflower herb.

For example, a tincture for oral administration can be prepared starting from 10 g of dry extract of passionflower herb (e.g. a 5:1 extract) made up to 200 g with a solvent of an alcohol/water mixture. The solvent mixture can be present, for example, in a ratio of 1 (alcohol): 1 to 10 (distilled water). The alcohol is, for example, ethanol or glycerol. The preparation is explained in detail in the examples. The tincture obtained can be taken, for example, once a day with, for example, 20 drops (20 drops are about 1 ml, 1 ml contains 50 mg of active ingredient for 10 g of dry extract) on a spoon or diluted further with water.

A tincture can also be made from 100 g of dry extract of passionflower herb (example: a 5:1 extract) diluted with a solvent to make 200 g of solution. The solvent is distilled water or a mixture of alcohol and distilled water. The tincture obtained can be taken, for example, once a day with, for example, 20 drops (20 drops are about 1 ml, 1 ml contains 500 mg of active ingredient) on a spoon or further diluted with water. The tincture can be taken one to five times a day, in some cases even six times a day, or one to four times a day, or one to three times a day, or once or twice a day, or even just once a day, depending on the clinical picture of the neurodermatitis. This depends on each individual case. For example, a tincture can also be made specifically for a patient at the appropriate dosage strength. The tincture is also available for purchase; for example, the tincture Ceres Passiflora Incarnata mother tincture from CERES Heilmittel GmbH or the tincture Naturalma passion flower (Passiflora incarnata) herb with blossoms, alcohol-free mother tincture from Naturalma srl, Bologna, come into question.

For oral administration in the form of a liquid dosage form, for example as a tincture, an amount of the dried mussel foot concentrate in the range from 0.20 to 6.0 g is preferably used for its preparation, which is made up to 200 g of solution, for example with a solvent . The solvent is distilled water or a mixture of alcohol and distilled water. The tincture obtained can be administered, for example, once a day with, for example, 20 drops (20 drops are then about 1 ml, 1 ml contains 1-30 mg of active substance).

• 10 - 100 g Trockenextrakt von Passionsblumenkraut (5 - 50 Gew.-%ige-Lösung, ergibt etwa 50 bis 500 mg in 20 Tropfen der Tinktur) und/oder
• 0,20 bis 6,0 g Miesmuschelfuß-Konzentrat (0,1 - 3,0 Gew.-%ige Lösung, ergibt etwa 1 bis 30 mg in 20 Tropfen der Tinktur),
• mit einem Lösungsmittel auf 200 g Lösung aufgefüllt, wobei das Lösungsmittel ausgewählt ist aus Wasser oder einer Alkohol/Wasser-Mischung mit einem Verhältnis von 1 : 1 bis 10.

Thus, a tincture for oral administration may preferably include:

• 10 - 100 g dry extract of passionflower herb (5 - 50% by weight solution, yields about 50 - 500 mg in 20 drops of the tincture) and/or
• 0.20 to 6.0 g of mussel foot concentrate (0.1 - 3.0% by weight solution, yields about 1 to 30 mg in 20 drops of the tincture),
• made up to 200 g solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of 1:1 to 10.

If the dry extract of the passion flower herb and the dried mussel foot concentrate are to be present together in the tincture, the quantities of both active ingredients are provided and filled up with solvent as already described.

For a tincture for topical administration, the preferred (dosage) amounts of the dried mussel foot concentrate and the dry passionflower herb extract, if present, are in the same ranges as for the tincture for oral administration. For the tincture for topical administration, it may be appropriate if a higher (dosage) amount is used (e.g. 27.5 - 50% by weight solution for the dry extract of the passion flower herb and 1.5 - 3.0% by weight % solution for the dried mussel foot concentrate), whereas for a tincture for oral administration the (dosage) amounts can be lower (e.g. 5 - 27.5% by weight solution for the dry extract of the passion flower herb and 0.1 - 1 .5% by weight solution for the dried mussel foot concentrate).

It should be noted here that the dry extracts of passionflower herb can differ in their dosage strength, since the concentration of the extracts can vary depending on the amount and type of passionflower herb starting material. As already explained, the usual concentrations are dry extracts of 5:1 to 7:1, although 10:1 can also be present. This is then taken into account by either adjusting the amount in the dosage form accordingly and/or increasing or decreasing the administration frequency, for example from 5 times daily to 3 times daily for a more concentrated extract present in the pharmaceutical composition. The amounts given here are usually based on the 5:1 extract, unless otherwise stated.

According to the invention, a mussel foot concentrate is always present in addition to the dry extract of the passion flower herb in the case of topical administration.

• 0,20 bis 6,0 g Miesmuschelfuß-Konzentrat (0,1 - 3,0 Gew.-%ige Lösung, ergibt etwa 1 bis 30 mg in 20 Tropfen der Tinktur),
• optional 10 - 100 g Trockenextrakt von Passionsblumenkraut (5 - 50 Gew.-%ige-Lösung, ergibt etwa 50 bis 500 mg in 20 Tropfen der Tinktur)
• mit einem Lösungsmittel auf 200 g Lösung aufgefüllt, wobei das Lösungsmittel ausgewählt ist aus Wasser oder einer Alkohol/Wasser-Mischung mit einem Verhältnis von 1 : 1 bis 10.

Thus, a tincture for topical administration may preferably include:

• 0.20 to 6.0 g of mussel foot concentrate (0.1 - 3.0% by weight solution, yields about 1 to 30 mg in 20 drops of the tincture),
• optional 10 - 100 g dry extract of passionflower herb (5 - 50% by weight solution, yields about 50 - 500 mg in 20 drops of the tincture)
• made up to 200 g solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of 1:1 to 10.

Another preferred dosage form for topical administration is a cream. According to one embodiment, the cream has the following components: dried mussel foot concentrate 0.5 - 10.00% by weight (particularly preferably based on mussels from the nature reserve Wadden Sea off Sylt) and optional dry extract of passionflower herb as well 0 - 50.00% by weight jojoba oil 5.00 - 25.00% by weight almond oil 1.00 - 15.00% by weight olive oil 1.00 - 8.00% by weight Temulsifier (vegetable emulsifier from palm oil) 1.00 - 10.00% by weight Shea butter (preferably refined) 1.00 - 10.00% by weight D-alpha-tocopheryl succinate (vitamin E) 0.10 - 2.00% by weight phenetyl alcohol 0.10 - 1.00% by weight essential oil(s) 0.10 - 2.00% by weight distilled water to 100% by weight.

The topical administration of the pharmaceutical composition can take place one to five times a day, in individual cases also more frequently, or one to four times a day or one to three times, once or twice a day or only once a day. The dosage is selected depending on the patient's body weight and the severity of the neurodermatitis. This depends on each individual case. For example, a dosage form can also be specially prepared for a patient with the appropriate dosage strength.

The total dose of the individual active ingredients is selected depending on the dosage form, the patient's body weight and the severity of the neurodermatitis. This depends on the individual case. If a combination preparation is used, the individual doses can be partially reduced.

The advantages of the present invention are extremely complex:
The pharmaceutical composition according to the invention is used in the therapeutic field for the treatment of neurodermatitis. The administration is orally or by application to the skin (topical) and is not particularly limited as to the administration form selected as long as the limitation according to the present invention is taken into account. The route of administration is preferably oral for a pharmaceutical composition comprising a dry extract of passionflower herb, also preferably oral for a combination of dry extract of passionflower herb and dried mussel foot concentrate, and preferably topical for dried mussel foot concentrate.

In a completely unexpected way, it was found that the active ingredients according to the invention, each or in combination, lead to particularly good treatment successes in neurodermatitis. A reduction in skin reddening, a significant reduction in itching, strengthening of the skin, reduced flaking of the skin, smoothing of the skin and an overall calming of the inflamed skin are observed. Overall, the treatment gives a better complexion. The pharmaceutical composition therefore has an overall positive effect on the skin and the complexion.

The adverse effects that occur with common drugs, such as glucocorticoids, such as thinning of the skin, skin changes or additional irritation can be completely avoided.

Particularly good treatment results can be achieved through the combined effect of dry extract from passion flower herb and dried mussel foot concentrate. The inflammation caused by neurodermatitis largely subsides within a short period of time.

Due to the significant improvement in the complexion, there is no need for additional administration of classic medicines.

The positive effect of the active ingredients on the skin is the focus overall, whereby the natural microflora of the skin is not damaged but rather remains intact. This increases skin elasticity, skin firmness, and the skin's water balance as well as cell differentiation and proliferation are positively influenced in the long term. In addition, the appearance of the skin is significantly improved.

In the following experimental part, some experiments are described in detail, in which the production and the therapeutic effectiveness of the pharmaceutical composition according to the invention are described. Of course, the present invention should not be limited thereby.

examples Preparation of some exemplary pharmaceutical dosage forms capsules

The ingredients used are given below:
Active ingredients: - Passion flower herb dry extract: (5:1 extract) and 400 mg - dried mussel foot concentrate: (based on mussels from the nature reserve Wadden Sea off Sylt) 5mg

Excipients: - Lactose monohydrate 5.0 mg - cellulose powder 5.0 mg - colloidal silica 5.0 mg - vegetable magnesium stearate 5.0 mg - vegan gelatine from red algae 5.0 mg - Sodium Lauryl Sulfate 5.0 mg - chlorophyllin copper complex (E 141) 5.0 mg - titanium dioxide (E171) 5.0 mg

Manufacturing:
The active ingredients are mixed together with the excipients and, if necessary, sieved. The finished mixture is packed into size 0 hard capsules (possible fill quantity 400 - 800 mg). Capsule filling: 445 mg

tablets

The ingredients used are listed below: Active ingredients: - Passion flower herb dry extract: (5:1 extract) and 400 mg - dried mussel foot concentrate: (based on mussels from the nature reserve Wadden Sea off Sylt) 5 mg

Excipients: - Lactose monohydrate 15.0 mg - cellulose powder 20.0 mg - colloidal silica 5.0 mg - vegetable magnesium stearate 5.0 mg - vegan gelatine from red algae 5.0 mg - Sodium Lauryl Sulfate 5.0 mg - chlorophyllin copper complex (E 141) 5.0 mg - titanium dioxide (E171) 5.0 mg

Manufacturing:
The active ingredients are mixed with all components, sieved and compressed in a tablet maker to form tablets of the desired shape. Tablet core weight: 470 mg Appearance of the tablet core: 10mm round

The tablet cores produced in this way are coated with a film consisting essentially of hydroxypropylmethylcellulose. Coated tablet weight: about 520 mg

tincture

Using the example of a tincture for oral administration from the dry extract of passion flower herb:
Manufacturing:
10 g dry extract of passion flower herb (5:1 extract) are poured to 200 g in a sealable container with a glycerin/water mixture (1:1). The container is sealed and left in a cool, dark place for at least four weeks. It is then filtered into a sterile, dark-tinted bottle. The obtained tincture can be administered orally directly or diluted with water.

cream

Using the example of a cream with the dried mussel foot concentrate:
A cream was made from the following ingredients: dried mussel foot concentrate 1.13% by weight (based on mussels from the nature reserve Wadden Sea off Sylt) jojoba oil 15.05% by weight almond oil 11.29% by weight olive oil 3.76% by weight Temulsifier (vegetable emulsifier from palm oil) 5.65% by weight refined shea butter 5.65% by weight D-alpha-tocopheryl succinate (vitamin E) 0.23% by weight phenetyl alcohol 0.30% by weight essential oil sea breeze 0.34% by weight volatile oil 0.15% by weight distilled water to 100% by weight

Try

Since March 2018, a series of trials to treat neurodermatitis have been carried out, which are still ongoing.

Tablets and tinctures (drops) with different concentrations of the active ingredients are tested, each for oral administration.

• LIORAN centra überzogene Tabletten von der Firma Niehaus Pharma GmbH & Co. KG:
  Wirkstoff: Passionsblumen-Trockenextrakt 425 mg pro 1 Tablette (Extrakt 5-7:1); Auszugsmittel: Ethanol 50% (Vol./Vol.). Weitere Bestandteile der Tablette gemäß den Herstellerangaben sind: Maltodextrin, Siliciumdioxid, hochdisperses Cellulosepulver, Croscarmellose-Natrium, Magnesiumstearat (pflanzlich), Stearinsäure (pflanzlich), Talkum, Saccharose, Calciumcarbonat, Gummi arabicum, Tragant, Glucose-Sirup, sprühgetrocknete Glucose, Hypromellose, Wachs, gebleichtes Carnaubawachs, Schellack, Titandioxid und Eisen(III)-oxidhydrat, gelb.
• PASSIO Balance überzogene Tabletten (Filmtabletten) von der Firma STADA Consumer Health Deutschland GmbH:
  Wirkstoff: Passionsblumen-Trockenextrakt 425 mg pro 1 Tablette (Extrakt 5-7:1); Auszugsmittel: Ethanol 50% (V/V). Weitere Bestandteile der Tablette gemäß den Herstellerangaben sind: Gummi arabicum, Calciumcarbonat, Carnaubawachs, Cellulosepulver, Croscarmellose-Natrium, Glucose-Sirup, sprühgetrocknete Hypromellose, Magnesiumstearat (pflanzlich), Maltodextrin, Schellack, Stearinsäure, Saccharose, Talkum, Tragant, Wachs, gebleichtes Siliciumdioxid, hochdisperses Eisen(III)-oxidhydrat, gelb und Titandioxid.
• PASCOFLAIR überzogene Tabletten (Filmtabletten) der Firma Pascoe pharmazeutische Präparate GmbH:
  Wirkstoff: Passionsblumen-Trockenextrakt 425 mg pro 1 Tablette (Extrakt 5-7:1); Auszugsmittel: Ethanol 50% (V/V). Weitere Bestandteile der Tablette gemäß den Herstellerangaben sind: Maltodextrin, Siliciumdioxid, hochdisperses Cellulosepulver, Croscarmellose-Natrium, Magnesiumstearat (pflanzlich), Stearinsäure, Talkum, Saccharose, Calciumcarbonat, Gummi arabicum, Tragant, Glucosesirup-Trockensubstanz, Hypromellose, Wachs, gebleichtes Carnaubawachs, Schellack und Eisen(III)-oxidhydrat, gelb.

The following commercially available tablets are used:

• LIORAN centra coated tablets from Niehaus Pharma GmbH & Co. KG:
  Active ingredient: passion flower dry extract 425 mg per 1 tablet (extract 5-7:1); Extraction agent: ethanol 50% (v/v). Other ingredients of the tablet according to the manufacturer's instructions are: maltodextrin, silicon dioxide, colloidal cellulose powder, croscarmellose sodium, magnesium stearate (vegetable source), stearic acid (vegetable source), talc, sucrose, calcium carbonate, gum arabic, tragacanth, glucose syrup, spray-dried glucose, hypromellose, Wax, bleached carnauba wax, shellac, titanium dioxide and hydrated iron(III) oxide, yellow.
• PASSIO Balance coated tablets (film tablets) from STADA Consumer Health Deutschland GmbH:
  Active ingredient: passion flower dry extract 425 mg per 1 tablet (extract 5-7:1); Extraction agent: ethanol 50% (v/v). Other ingredients of the tablet according to the manufacturer's instructions are: gum arabic, calcium carbonate, carnauba wax, cellulose powder, croscarmellose sodium, glucose syrup, spray-dried hypromellose, magnesium stearate (vegetable), maltodextrin, shellac, stearic acid, sucrose, talc, tragacanth, wax, bleached silicon dioxide , colloidal ferric oxide hydrate, yellow and titanium dioxide.
• PASCOFLAIR coated tablets (film tablets) from Pascoe pharmaceutical preparations GmbH:
  Active ingredient: passion flower dry extract 425 mg per 1 tablet (extract 5-7:1); Extraction agent: ethanol 50% (v/v). Other ingredients of the tablet according to the manufacturer's instructions are: maltodextrin, silicon dioxide, colloidal anhydrous cellulose powder, croscarmellose sodium, magnesium stearate (vegetable source), stearic acid, talc, sucrose, calcium carbonate, gum arabic, tragacanth, glucose syrup solids, hypromellose, wax, bleached carnauba wax, shellac and iron(III) oxide hydrate, yellow.

A commercial product was selected from each of the above tablets and 3 tablets thereof were administered to a patient daily.

Alternatively, a tincture was administered.

• Naturalma Passionsblume (Passiflora incarnata), Kraut mit Blüten, Alkoholfreie Urtinktur von der Firma Naturalma srl, Bologna.

The following commercially available tincture is used:

• Naturalma passion flower (Passiflora incarnata), herb with flowers, alcohol-free mother tincture from Naturalma srl, Bologna.

According to the manufacturer's information, the ingredients are: vegetable glycerin, pure water, passion flower (Passiflora incarnata), herb with flowers; concentrated 1:10; 40 drops (2 ml) contain 200 mg passion flower.

Become of the tincture
40 drops administered five to six times a day.

The treatment with the tablets and the tincture resulted in a significantly improved complexion. The skin appeared less inflamed, softer, smoother, less redness is visible. Overall, the complexion is calmer and more stable and is getting closer and closer to the complexion of a healthy person.

Treatment with the tablets and tincture usually led to a significant improvement in the complexion after just 7 to 14 days of treatment. This is particularly evident in neurodermatitis that occurs on the face. As a result of the treatment, a fading of the redness and a reduction in the inflammation are observed. The facial skin seems to regenerate and after a few days it can hardly be distinguished from that of a healthy person.

Thus, according to the invention, a pharmaceutical composition is provided for the first time, comprising a plant and/or animal active substance for the treatment of neurodermatitis by oral administration. In addition, topical application, based on an animal active substance, optionally together with a plant-based active substance, is also possible. The effectiveness is surprisingly high, although the disadvantages of classic drugs do not occur. Rather, there is a high level of tolerability during use, with the properties of the skin being even positively influenced at the same time.

The invention includes aspects disclosed in the following sentences which form part of the description but do not form the claims.

sentences

• wobei der Trockenextrakt des Passionsblumenkrauts von Passionsblumen aus biologischem Anbau ist und/oder
• dass das getrocknete Miesmuschelfuß-Konzentrat von Miesmuscheln aus einem Naturschutzgebiet ist.

10. Pharmazeutische Zusammensetzung nach einem der vorangehenden Sätze 1 bis 9,
wobei eine orale Dosierungsform

• Passionsblumenkraut in Form eines Trockenextrakts und optional einen oder mehrere pharmazeutisch akzeptable Hilfsstoffe aufweist; oder
• Passionsblumenkraut in Form eines Trockenextrakts und getrocknetes Miesmuschelfuß-Konzentrat und optional einen oder mehrere pharmazeutisch akzeptable Hilfsstoffe aufweist; oder
• getrocknetes Miesmuschelfuß-Konzentrat und optional einen oder mehrere pharmazeutisch akzeptable Hilfsstoffe aufweist.

11. Pharmazeutische Zusammensetzung nach einem der vorangehenden Sätze 1 bis 9,
wobei eine topische Dosierungsform getrocknetes Miesmuschelfuß-Konzentrat aufweist und gegebenenfalls Passionsblumenkraut in Form eines Trockenextrakts sowie einen oder mehrere pharmazeutisch akzeptable Hilfsstoffe.
12. Pharmazeutische Zusammensetzung nach einem der vorangehenden Sätze 10 oder 11,
wobei nur vegane Hilfsstoffe, insbesondere nur pflanzliche Hilfsstoffe eingesetzt werden.
13. Pharmazeutische Zusammensetzung nach einem der vorangehenden Sätze 1 bis 12,
wobei eine Dosierungsform ausgewählt wird aus:
einer Kapsel, umfassend - Trockenextrakt aus Passionsblumenkraut: 5,0 - 99,9 Gew.-% und - getrocknetes Miesmuschelfuß-Konzentrat: 0,1 - 10,0 Gew.-%, oder - Trockenextrakt aus Passionsblumenkraut: 5,0 - 100 Gew.-% oder - getrocknetes Miesmuschelfuß-Konzentrat: 0,1 - 100 Gew.-% und optional die folgenden Hilfsstoffe: - Lactose-Monohydrat 0 - 45,0 Gew.-% - Cellulosepulver 0 - 45,0 Gew.-% - hochdisperses Siliciumdioxid 0 - 5,0 Gew.-% - pflanzliches Magnesiumstearat 0 - 5,0 Gew.-% - vegane Gelatine aus Rotalgen 0 - 5,0 Gew.-% - Natriumdodecylsulfat 0 - 5,0 Gew.-% - Chlorophyllin-Kupfer-Komplex (E 141) 0 - 2,0 Gew.-% - Titandioxid (E171) 0 - 5,0 Gew.-%, wobei die Mengen der jeweiligen Komponenten so gewählt sind, dass das Gesamtgewicht der Komponenten 100 Gew.-% nicht übersteigt; oder
einer Tablette, umfassend - Trockenextrakt aus Passionsblumenkraut: 5,0 - 93,4 Gew.-% und - getrocknetes Miesmuschelfuß-Konzentrat: 0,1 - 10 Gew.-%, oder - Trockenextrakt aus Passionsblumenkraut: 5,0 - 93,5 Gew.-% oder - getrocknetes Miesmuschelfuß-Konzentrat: 0,1 - 93,5 Gew.-% und die folgenden Hilfsstoffe: - Lactose-Monohydrat 2,5 - 45,0 Gew.-% - Cellulosepulver 3,5 - 45,0 Gew.-% - hochdisperses Siliciumdioxid 0 - 5,0 Gew.-% - pflanzliches Magnesiumstearat 0,5 - 5,0 Gew.-% - vegane Gelatine aus Rotalgen 0 - 5,0 Gew.-% - Natriumdodecylsulfat 0 - 5,0 Gew.-% - Chlorophyllin-Kupfer-Komplex (E 141) 0 - 2,0 Gew.-% - Titandioxid (E171) 0 - 5,0 Gew.-%, wobei die Mengen der jeweiligen Komponenten so gewählt sind, dass das Gesamtgewicht der Komponenten 100 Gew.-% nicht übersteigt;
sowie optional eine zusätzliche Beschichtung der Tablette; oder
einer Tinktur zur oralen Verabreichung, umfassend
10 - 100 g Trockenextrakt von Passionsblumenkraut und/oder
0,20 bis 6,0 g Miesmuschelfuß-Konzentrat,
mit einem Lösungsmittel auf 200 g Lösung aufgefüllt, wobei das Lösungsmittel ausgewählt ist aus Wasser oder einer Alkohol/Wasser-Mischung mit einem Verhältnis von 1 : 1 bis 10; oder
einer Tinktur zur topischen Verabreichung, umfassend
0,20 bis 6,0 g Miesmuschelfuß-Konzentrat und
optional 10 - 100 g Trockenextrakt von Passionsblumenkraut,
mit einem Lösungsmittel auf 200 g Lösung aufgefüllt, wobei das Lösungsmittel ausgewählt ist aus Wasser oder einer Alkohol/Wasser-Mischung mit einem Verhältnis von 1 : 1 bis 10; oder
einer Creme, umfassend getrocknetes Miesmuschelfuß-Konzentrat 0,5 - 10,00 Gew.-% und optional Trockenextrakt von Passionsblumenkraut sowie 0 - 50,00 Gew.-% Jojobaöl 5,00 - 25,00 Gew.-% Mandelöl 1,00 - 15,00 Gew.-% Olivenöl 1,00 - 8,00 Gew.-% Temulgator (pflanzlicher Emulgator aus Palmöl) 1,00 - 10,00 Gew.-% Sheabutter (bevorzugt raffiniert) 1,00 - 10,00 Gew.-% D-alpha-Tocopherylsuccinat (Vitamin E) 0,10 - 2,00 Gew.-% Phenetylalkohol 0,10 - 1,00 Gew.-% ätherische(s) Öl(e) 0,10 - 2,00 Gew.-% destilliertes Wasser auf 100 Gew.-%, wobei die Mengen der jeweiligen Komponenten so gewählt sind, dass das Gesamtgewicht der Komponenten 100 Gew.-% nicht übersteigt.1. A pharmaceutical composition comprising passionflower herb in the form of a dry extract as an active ingredient and/or dried mussel foot concentrate as a further active ingredient, for use in the treatment of neurodermatitis by oral or topical administration, with the proviso that passionflower herb in the form of a dry extract only together applied topically with dried mussel foot concentrate.
2. pharmaceutical composition according to sentence 1,
wherein the oral dosage form is selected from tablets, in particular film-coated tablets, pills, coated tablets, lozenges, pellets, capsules, in particular hard or soft capsules, powder, granules, solutions, in particular tinctures in the form of drops, suspensions, dispersions or emulsions, preferably film-coated tablets, Capsules, tinctures in the form of drops.
3. Pharmaceutical composition according to one of the preceding sentences 1 or 2,
wherein the topical dosage form is selected from a solution, especially a tincture in the form of drops, an oil, a suspension, especially a shake-up, dispersion, emulsion, lotion or milk, a cream or paste, preferably a tincture in the form of drops or a cream.
4. Pharmaceutical composition according to one of the preceding sentences 1 to 3,
wherein the amount, per dosage form, for oral administration of the dry extract of passion flower herb ranges from 45 to 500 mg, or 90 to 450 mg, or 100 to 450 mg, or 150 to 450 mg, or 200 to 450 mg, or 250 to 450 mg.
5. Pharmaceutical composition according to one of the preceding sentences 1 to 4,
wherein the total dose for oral administration of the dry extract of passionflower herb ranges from 45 to 2500 mg, or 90 to 2250 mg, or 100 to 2000 mg, or 225 to 1800 mg, or 400 to 1500 mg for one patient per day.
6. Pharmaceutical composition according to one of the preceding sentences 1 to 5,
wherein the amount, per dosage form, for oral administration of the dried mussel foot concentrate ranges from 1 mg to 50 mg, or 1 to 30 mg, or 1 to 15 mg, or 2 to 12 mg, or 3 to 10 mg.
7. Pharmaceutical composition according to one of the preceding sentences 1 to 6,
wherein the total dose for the dried mussel foot concentrate ranges from about 5 to 250 mg, or 10 to 200 mg, or 15 to 150 mg, or 15 to 100 mg for one patient per day.
8. Pharmaceutical composition according to one of the preceding sentences 1 to 7,
wherein the dry extract of the passion flower herb as an active ingredient and the dried mussel foot concentrate as a further active ingredient are administered as a fixed dose combination, with the two active ingredients being present simultaneously in the same pharmaceutical formulation, or as a free dose combination, with the two active ingredients being present in separate pharmaceutical formulations which can be the same or different.
9. Pharmaceutical composition according to one of the preceding sentences 1 to 8,

• wherein the dry extract of the passion flower herb is from passion flowers from organic cultivation and/or
• that the dried mussel foot concentrate is made from mussels from a nature reserve.

10. Pharmaceutical composition according to one of the preceding sentences 1 to 9,
being an oral dosage form

• passion flower herb in the form of a dry extract and optionally one or more pharmaceutically acceptable excipients; or
• passion flower herb in the form of a dry extract and dried mussel foot concentrate and optionally one or more pharmaceutically acceptable excipients; or
• dried mussel foot concentrate and optionally one or more pharmaceutically acceptable excipients.

11. Pharmaceutical composition according to one of the preceding sentences 1 to 9,
wherein a topical dosage form comprises dried mussel foot concentrate and optionally passionflower herb in the form of a dry extract and one or more pharmaceutically acceptable excipients.
12. Pharmaceutical composition according to one of the preceding sentences 10 or 11,
whereby only vegan excipients, in particular only plant-based excipients, are used.
13. Pharmaceutical composition according to one of the preceding sentences 1 to 12,
wherein a dosage form is selected from:
a capsule comprising - Dry extract of passion flower herb: 5.0 - 99.9% by weight and - dried mussel foot concentrate: 0.1 - 10.0% by weight, or - Dry extract of passion flower herb: 5.0 - 100% by weight or - dried mussel foot concentrate: 0.1 - 100% by weight and optionally the following excipients: - Lactose monohydrate 0 - 45.0% by weight - cellulose powder 0 - 45.0% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight, wherein the amounts of the respective components are chosen such that the total weight of the components does not exceed 100% by weight; or
a tablet comprising - Dry extract of passion flower herb: 5.0 - 93.4% by weight and - dried mussel foot concentrate: 0.1 - 10% by weight, or - Dry extract of passion flower herb: 5.0 - 93.5% by weight or - dried mussel foot concentrate: 0.1 - 93.5% by weight and the following excipients: - Lactose monohydrate 2.5 - 45.0% by weight - cellulose powder 3.5 - 45.0% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0.5 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight, wherein the amounts of the respective components are chosen such that the total weight of the components does not exceed 100% by weight;
and optionally an additional coating of the tablet; or
a tincture for oral administration comprising
10 - 100 g dry extract of passion flower herb and/or
0.20 to 6.0 g mussel foot concentrate,
made up to 200 g of solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of from 1:1 to 10; or
a tincture for topical administration comprising
0.20 to 6.0 g of mussel foot concentrate and
optionally 10 - 100 g dry extract of passion flower herb,
made up to 200 g of solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of from 1:1 to 10; or
a cream comprising dried mussel foot concentrate 0.5 - 10.00% by weight and optional dry extract of passionflower herb as well 0 - 50.00% by weight jojoba oil 5.00 - 25.00% by weight almond oil 1.00 - 15.00% by weight olive oil 1.00 - 8.00% by weight Temulsifier (vegetable emulsifier from palm oil) 1.00 - 10.00% by weight Shea butter (preferably refined) 1.00 - 10.00% by weight D-alpha-tocopheryl succinate (vitamin E) 0.10 - 2.00% by weight phenetyl alcohol 0.10 - 1.00% by weight essential oil(s) 0.10 - 2.00% by weight distilled water to 100% by weight, the amounts of the respective components being chosen such that the total weight of the components does not exceed 100% by weight.

Claims (13)

A pharmaceutical composition comprising Passion flower herb in the form of a dry extract as an active ingredient and/or dried mussel foot concentrate as an additional active ingredient, for use in the treatment of neurodermatitis by oral or topical administration, wherein the passion flower herb is available in the form of a dry extract from - Harvesting, crushing and drying of the passion flower herb in the form of the plant parts of the passion flower, without the root; - Carrying out a solid-liquid extraction of the dried plant parts using an extractant selected from water, alcohol or alcohol-water mixtures at room temperature or a temperature in the range between room temperature and 78°C, with or without stirring and/or shaking ; - separating the plant parts from the extractant by decantation or filtration, and - evaporating the extraction agent to obtain a dry extract of passion flower herb; and wherein the dried mussel foot concentrate is crushed and dried mussel foot from mussels, with the proviso that passion flower herb is administered topically in the form of a dry extract only together with dried mussel foot concentrate and that Candida albicans and N,N-dimethylglycine are not included in the pharmaceutical composition. Pharmaceutical composition according to claim 1,
characterized,
that the oral dosage form is selected from tablets, in particular film-coated tablets, pills, coated tablets, lozenges, pellets, capsules, in particular hard or soft capsules, powder, granules, solutions, in particular tinctures in the form of drops, suspensions, dispersions or emulsions, preferably film-coated tablets, Capsules, tinctures in the form of drops. Pharmaceutical composition according to any one of the preceding claims 1 or 2,
characterized,
that the topical dosage form is selected from a solution, in particular as a tincture in the form of drops, oil, suspension, in particular a shaking mix, dispersion, emulsion, lotion or milk, cream or paste, preferably a tincture in the form of drops or cream. Pharmaceutical composition according to any one of the preceding claims 1 to 3,
characterized,
that the amount, per dosage form, for oral administration of the dry extract of passion flower herb is in the range of 45 to 500 mg, or 90 to 450 mg, or 100 to 450 mg, or 150 to 450 mg, or 200 to 450 mg, or 250 to 450 mg. Pharmaceutical composition according to any one of the preceding claims 1 to 4,
characterized,
that the total dose for oral administration of the dry extract of passion flower herb ranges from 45 to 2500 mg, or 90 to 2250 mg, or 100 to 2000 mg, or 225 to 1800 mg, or 400 to 1500 mg for one patient per day. Pharmaceutical composition according to any one of the preceding claims 1 to 5,
characterized,
that the amount, per dosage form, for oral administration of the dried mussel foot concentrate ranges from 1 mg to 50 mg, or 1 to 30 mg, or 1 to 15 mg, or 2 to 12 mg, or 3 to 10 mg. Pharmaceutical composition according to any one of the preceding claims 1 to 6,
characterized,
that the total dose for the dried mussel foot concentrate is in the range of about 5 to 250 mg, or 10 to 200 mg, or 15 to 150 mg, or 15 to 100 mg for one patient per day. Pharmaceutical composition according to any one of the preceding claims 1 to 7,
characterized,
that the dry extract of the passion flower herb as an active ingredient and the dried mussel foot concentrate as a further active ingredient are administered as a fixed dose combination, with the two active ingredients being present simultaneously in the same pharmaceutical formulation, or as a free dose combination, with the two active ingredients being present in separate pharmaceutical formulations which can be the same or different. Pharmaceutical composition according to any one of the preceding claims 1 to 8,
characterized,
that the dry extract of the passion flower herb is from passion flowers from organic farming and/or
that the dried mussel foot concentrate is made from mussels from a nature reserve. Pharmaceutical composition according to any one of the preceding claims 1 to 9,
characterized,
that an oral dosage form - Passiflora herb in the form of a dry extract and optionally one or more pharmaceutically acceptable excipients; or - Passiflora herb in the form of a dry extract and dried mussel foot concentrate and optionally one or more pharmaceutically acceptable excipients; or - dried mussel foot concentrate and optionally one or more pharmaceutically acceptable excipients. Pharmaceutical composition according to any one of the preceding claims 1 to 9,
characterized,
that a topical dosage form comprises dried mussel foot concentrate and optionally passionflower herb in the form of a dry extract and one or more pharmaceutically acceptable excipients. Pharmaceutical composition according to any one of the preceding claims 10 or 11,
characterized,
that only vegan excipients, in particular only plant-based excipients, are used. Pharmaceutical composition according to any one of the preceding claims 1 to 12,
characterized,
that a dosage form is selected from: a capsule comprising - Dry extract of passion flower herb: 5.0 - 99.9% by weight and - dried mussel foot concentrate: 0.1 - 10.0% by weight, or - Dry extract of passion flower herb: 5.0 - 100% by weight or - dried mussel foot concentrate: 0.1 - 100% by weight and optionally the following excipients: - Lactose monohydrate 0 - 45.0% by weight - cellulose powder 0 - 45.0% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight, wherein the amounts of the respective components are chosen such that the total weight of the components does not exceed 100% by weight; or a tablet comprising - Dry extract of passion flower herb: 5.0 - 93.4% by weight and - dried mussel foot concentrate: 0.1 - 10% by weight, or - Dry extract of passion flower herb: 5.0 - 93.5% by weight or - dried mussel foot concentrate: 0.1 - 93.5% by weight and the following excipients: - Lactose monohydrate 2.5 - 45.0% by weight - cellulose powder 3.5 - 45.0% by weight - colloidal silica 0 - 5.0% by weight - vegetable magnesium stearate 0.5 - 5.0% by weight - vegan gelatine from red algae 0 - 5.0% by weight - Sodium Lauryl Sulfate 0 - 5.0% by weight - chlorophyllin copper complex (E 141) 0 - 2.0% by weight - titanium dioxide (E171) 0 - 5.0% by weight, wherein the amounts of the respective components are chosen such that the total weight of the components does not exceed 100% by weight; and optionally an additional coating of the tablet; or a tincture for oral administration comprising 10 - 100 g dry extract of passion flower herb and/or 0.20 to 6.0 g mussel foot concentrate, made up to 200 g of solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of from 1:1 to 10; or
a tincture for topical administration comprising 0.20 to 6.0 g of mussel foot concentrate and optionally 10 - 100 g dry extract of passion flower herb, made up to 200 g of solution with a solvent, the solvent being selected from water or an alcohol/water mixture with a ratio of from 1:1 to 10; or a cream comprising dried mussel foot concentrate 0.5 - 10.00% by weight and optional dry extract of passionflower herb as well 0 - 50.00% by weight jojoba oil 5.00 - 25.00% by weight almond oil 1.00 - 15.00% by weight olive oil 1.00 - 8.00% by weight Temulsifier (vegetable emulsifier from palm oil) 1.00 - 10.00% by weight Shea butter (preferably refined) 1.00 - 10.00% by weight D-alpha-tocopheryl succinate (vitamin E) 0.10 - 2.00% by weight phenetyl alcohol 0.10 - 1.00% by weight essential oil(s) 0.10 - 2.00% by weight distilled water to 100% by weight, the amounts of the respective components being chosen such that the total weight of the components does not exceed 100% by weight.